d-galactose induces premature senescence of lens epithelial cells by disturbing autophagy flux and mitochondrial functions.

Cataract is the leading cause of blindness with an estimated 16 million people affected worldwide. d-galactose (d-gal) is a reducing sugar that widely distributed in foodstuffs, and studies show that d-gal could promote cataract formation by damaging nature lens epithelial cells (LECs). However, the underlying mechanism is unclear. In our present study, d-gal resulted in premature senescence of LECs, which was confirmed by determining the β-galactosidase activity, cell proliferative potential and cell cycle distribution, though apoptosis of LECs was not observed. We also verified that d-gal induced the impairment of autophagy flux by measuring the expression of LC3II and P62. Meanwhile, we found that d-gal induced mitochondrial dysfunctions of LECs through increasing reactive oxygen species (ROS), reducing ATP synthesis and mitochondrial potential (MMP), enhancing the concentration of cytoplasm Ca2+ and permeability transition pore (mPTP) opening. Metformin, as a potential anti-aging agent, suppressed the senescence of LECs by restoring autophagy flux and mitochondria functions. Nevertheless, the antioxidant N-acetylcysteine (NAC) scavenged ROS significantly but was not efficient in preventing LECs from premature senescence. Our data suggests that restoring autophagy activity and improving mitochondrial functions may be a potential strategy for the prevention of LECs senescence-related cataract.